Autobiographical Memory, Future Thought, and Eye Movements in Huntington's Disease

Mémoire Autobiographique, pensée Future et Mouvements OCulaires Dans la Maladie de Huntington - MAMOC-MH

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by progressively worsening motor, cognitive, psychiatric, and behavioral deficits. Cognitive deficits occur early on, affecting in particular executive functions (inhibition, flexibility), decision-making, memory, attention (selective, sustained), perceptual and visuospatial skills, and information processing speed.

More specifically, memory deficits quickly affect different memory systems (short-term memory, long-term memory, etc.), including autobiographical memory. Autobiographical memory is usually defined as a system that stores all the information (semantic component) and specific memories (episodic component) specific to an individual, accumulated from an early age. Autobiographical memory is now considered essential to the construction of a sense of identity and continuity. It is also considered indispensable for projecting into the future, otherwise known as "episodic future thinking," a fundamental human capacity that is both anticipatory and adaptive.

Autobiographical memory deficits remain largely unexplored in HD, with only three studies identified in the international literature on the subject, one of which is actually based on the same neuropsychological data as another, adding a neuroanatomical analysis focused on autobiographical memory. These studies show that the autobiographical recollections of patients with HD are mainly descriptive recollections of personal events lacking in detail, and that the abnormalities appear to be linked to the progressive degeneration of a vast cortico-subcortical brain network comprising the medial temporal cortex, the frontal cortex, and the posterior striatal and parietal regions. Deficits in episodic future thinking have never been explored in HD. A better understanding of the mechanisms underlying this type of cognitive impairment (recalling personal memories and mentally simulating future personal events) remains a major challenge today in improving the care of patients with HD.

Several recent studies have shown, in different pathological contexts (Alzheimer's disease, etc.), that the parallel use of neuropsychological tests (tasks and questionnaires) and an eye-tracking system allows for a much more accurate and in-depth examination of cognitive functions (for a review, see). In addition, eye movements, such as fixations and saccades, have been associated with the retrieval of autobiographical events . These movements better reflected the person's subjective experience, particularly with regard to the visual elements of mental imagery of recovered events. This suggests that the analysis of eye behavior could enrich the assessment of autobiographical memory, beyond the data provided by traditional tests.

The examination of eye movements is therefore, alongside neuropsychological testing, a promising non-invasive method for better understanding the characteristics of autobiographical memory in HD.

This project therefore aims to explore the autobiographical memory of HD patients by analyzing their eye activity during tasks involving the recall of personal events using standard neuropsychological tools. By identifying oculomotor markers associated with autobiographical memory disorders, this research could: (1) provide a better understanding of the neurocognitive profile of HD, (2) pave the way for more accurate diagnostic tools, and (3) form an important basis for the development of future interventions aimed at supporting memory function in this population.

Inclusion criteria

For patients:

• Adults at inclusion
• Huntington's disease diagnosed and confirmed by genetic analysis
• Patients in the presymptomatic stage of HD with a motor UHDRS score ≤ 5 and patients in symptomatic stages 1-2 of HD with a motor UHDRS score > 5 and a CFT between 6 < CFT ≤ 13
• Patients who have given their written informed consent or consent from a third party
• Affiliated with or beneficiary of a social security system

For healthy controls:

Pre-inclusion criteria

• Adults at inclusion
• Individuals with no history of neurological disorders (interview and clinical examination)
• Signature of informed consent to participate in the study
• Affiliated with or beneficiary of a social security system
• Matching in age (± 5 years), sex, and level of education with an HD patient included in the control group

Inclusion criteria

• MMSE ≥ 24/30